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Dev Cell. 2017 May 8;41(3):228-241. doi: 10.1016/j.devcel.2017.04.001.

The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force.

Author information

1
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Electronic address: kovallra@ucmail.uc.edu.
2
Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
3
Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
4
Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: raphael.kopan@cchmc.org.

Abstract

The Notch signaling pathway relies on a proteolytic cascade to release its transcriptionally active intracellular domain, on force to unfold a protective domain and permit proteolysis, on extracellular domain glycosylation to tune the forces exerted by endocytosed ligands, and on a motley crew of nuclear proteins, chromatin modifiers, ubiquitin ligases, and a few kinases to regulate activity and half-life. Herein we provide a review of recent molecular insights into how Notch signals are triggered and how cell shape affects these events, and we use the new insights to illuminate a few perplexing observations.

KEYWORDS:

Notch signaling; mechanism; review; transcription

PMID:
28486129
PMCID:
PMC5492985
DOI:
10.1016/j.devcel.2017.04.001
[Indexed for MEDLINE]
Free PMC Article

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